title: Excitotoxic neurodegeneration induced by deprivation of oxygen and glucose in isolated retina.
abstract: OBJECTIVE
  Ischemic neurodegeneration contributes to many retinal diseases. An isolated retina model has been used to examine the neuronal cell death induced by deprivation of oxygen and glucose (simulated ischemia) as a model for ischemic disease.
  
  
  METHODS
  Neurodegeneration in the isolated chick embryo retina was induced by simulated ischemia and assessed using biochemical (lactate dehydrogenase release) and morphologic (light microscopy) techniques.
  
  
  RESULTS
  Simulated ischemia led to lactate dehydrogenase release gradually in a period of 6 to 24 hours. Light microscopic observations demonstrated morphologic cell degeneration well before lactate dehydrogenase release occurred. N-Methyl-D-aspartate (NMDA) and non-NMDA receptor blockers individually provided partial protection, and the combination was fully protective. No protection was provided if the antagonists were added after simulated ischemia. When NMDA receptors were blocked by MK-801, cyclothiazide, an inhibitor of desensitization at non-NMDA receptors, enhanced lactate dehydrogenase released after 1 or 2 hours of simulated ischemia. Low concentrations of glucose effectively prevented lactate dehydrogenase release, despite anoxic conditions.
  
  
  CONCLUSIONS
  The isolated retina provided a convenient system to characterize quantitatively ischemic cell death. Retinal ischemic neurodegeneration is an excitotoxic process that involves overactivation of NMDA and non-NMDA glutamate receptors. Blockade of both of these receptor subtypes was necessary for complete neuroprotection. Receptor desensitization played a protective role. If even low concentrations of glucose were delivered to an ischemic retina in vitro, substantial neuroprotection could be achieved. This may have implications for the management of acute retinal ischemic episodes.
authors.affiliation: Department of Ophthalmology and Visual Sciences 63110, USA.
authors.forename: C
authors.initials: C
authors.lastname: Romano
authors.forename: M T
authors.initials: MT
authors.lastname: Price
authors.forename: T
authors.initials: T
authors.lastname: Almli
authors.forename: J W
authors.initials: JW
authors.lastname: Olney
mesh_terms: D000818:Animals; D016923:Cell Death; D002642:Chick Embryo; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007511:Ischemia / Q000150:complications / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009410:Nerve Degeneration; D010100:Oxygen / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012162:Retinal Degeneration / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D010100:Oxygen